WBSCR16 Is a Guanine Nucleotide Exchange Factor Important for Mitochondrial Fusion

Publication date: 25 July 2017
Source:Cell Reports, Volume 20, Issue 4
Author(s): Guorui Huang, Dawiyat Massoudi, Alison M. Muir, Dinesh C. Joshi, Chuan-Li Zhang, Shing Yan Chiu, Daniel S. Greenspan
Regulated inter-mitochondrial fusion/fission is essential for maintaining optimal mitochondrial respiration and control of apoptosis and autophagy. In mammals, mitochondrial fusion is controlled by outer membrane GTPases MFN1 and MFN2 and by inner membrane (IM) GTPase OPA1. Disordered mitochondrial fusion/fission contributes to various pathologies, and MFN2 or OPA1 mutations underlie neurodegenerative diseases. Here, we show that the WBSCR16 protein is primarily associated with the outer face of the inner mitochondrial membrane and is important for mitochondrial fusion. We provide evidence of a WBSCR16/OPA1 physical interaction in the intact cell and of a WBSCR16 function as an OPA1-specific guanine nucleotide exchange factor (GEF). Homozygosity for a Wbscr16 mutation causes early embryonic lethality, whereas neurons of mice heterozygous for the mutation have mitochondria with reduced membrane potential and increased susceptibility to fragmentation upon exposure to stress, suggesting roles for WBSCR16 deficits in neuronal pathologies.

Graphical abstract

Teaser

Mitochondrial GTPase OPA1 is essential to inter-mitochondrial fusion, which is essential to mitochondrial function. Huang et al. show that WBSCR16 is closely associated with OPA1 on the outer face of the mitochondrial inner membrane, acts as an OPA1-specific guanine nucleotide exchange factor (GEF), and is important for mitochondrial fusion.


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